Data-driven statistical approaches, such as cluster analysis or independent component analysis, applied to in vivo functional neuroimaging data help to identify neural processing networks that exhibit similar task-related or restingstate patterns of activity. Ideally, the measured brain activity for voxels within such networks should exhibit high autocorrelation. An important limitation is that the algorithms do not typically quantify or statistically test the strength or nature of the within-network relatedness between voxels. To extend the results given by such data-driven analyses, we propose the use of Moran’s I statistic to measure the degree of functional autocorrelation within identified neural processing networks and to evaluate the statistical significance of the observed associations. We adapt the conventional definition of Moran’s I, for applicability to neuroimaging analyses, by defining the global autocorrelation index using network-based neighborhoods. Also, we compute network-specific contributions to the overall autocorrelation. We present results from a bootstrap analysis that provide empirical support for the use of our hypothesis testing framework. We illustrate our methodology using positron emission tomography (PET) data from a study that examines the neural representation of working memory among individuals with schizophrenia and functional magnetic resonance imaging (fMRI) data from a study of depression.